RBI-257: A highly potent dopamine D-4 receptor-selective ligand

RBI-257 (1-[4-iodobenzyl]-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine), the p-iodobenzyl analog of U-101,958 (1- benzyl-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine had a lower dissociation constant (K-i = 0.3 vs. 2.7 nM) and higher selectivity than U-101,958 at dopamine D-4 receptors, over dopamine D-2 and D-3 receptors in transfected cell membranes and D-2-like sites in rat forebrain. Dopamine D-4 receptor affinity of iodo-isomers of RBI-257 ranked: para > meta > ortho. RBI-257 had much lower affinity at D-1 and D-5 dopamine receptors in transfected cells, as well as dopamine D-1-like receptors, alpha(1), alpha(2) or beta(1,2) adrenoceptors, sigma(1,2) receptors and 5-HT1A or 5-HT2A receptors, and transporters for dopamine, norepinephrine or serotonin in rat forebrain tissue. RBI-257 may be a useful probe or radioligand for brain dopamine D-4 receptors. (C) 1997 Elsevier Science B.V.